In many applications, filters are employed as substrates to facilitate animal cell growth. By way of example, cells may be grown on a filter support that is held, either vertically or horizontally, between two chambers. Once a cell monolayer is grown upon one side of the filter located between the two chambers, a variety of measurements can be made to characterize the cells, including, permeability of the cell layers, the ability of drugs to pass through the cell layer, the ability of cells to move through the filter, etc. These measurements may be made electrically, with the use of labeled compounds, such as dyes or radioisotopes, or simply by microscopically observing the cells.
One form of measuring cell behavior employs electrical sensing. One example of this is disclosed in U.S. Letters Pat. No. 5,187,096, which is hereby incorporated herein by reference, and referred to herein as the “ECIS® system”. Specifically, the ECIS® system (Electric Cell-substrate Impedance Sensing), which is marketed by Applied BioPhysics, Inc., of Troy, N.Y., U.S.A., passively analyzes cell behavior by applying a weak AC current, and measuring voltage changes. The device can be used to monitor various cell behaviors, including morphology changes and cell motions in animal cells that are attached and spread out and crawl, for example, on the bottom of a tissue culture vessel. In the ECIS®system, cells are typically grown upon one or more small gold film electrodes (e.g., each 5×10−4 to 10×10−4 cm2 in size), mounted to the bottom of a small well with (in one embodiment) a much larger counter-electrode completing the circuit using a standard tissue culture medium as an electrolyte. A weak (e.g., approximately 2 microamp) AC current (usually in the frequency range of 100 to 100,000 Hz) is applied to the electrode. This small current results in a voltage drop across the small, active electrode of only a few millivolts. Voltage drops this small do not affect the health of the cells.
Variations in the measured voltage comprise the measurement. As animal cells attach and spread upon the small, active electrode, they force the current to flow under and between the cells, resulting in changes in impedance, and hence, in the measured voltage across the electrodes. These changes can be followed and provide a non-invasive means to monitor changes in cell behavior. For example, using the measured voltages, one can infer cell morphology and cell movements, which are important research measurements that form the basis of many biomedical and biological assays.
Additionally, transepithelial resistance (TER) measurement has been used to study paracelluar transport properties of epithelia grown on permeable filters, especially the barrier function of tight junctions. The permeable filters are usually porated (track-etched pores), but can also be tortuous-path filters. Differences in making measurements in cell permeability with different types of filter supports is described by Lo et al. in a paper entitled, “Rapid Communication, Cell-Substrate Contact: Another Factor May Influence Transepithelial Electrical Resistance of Cell Layers Cultured on Permeable Filters”, Experimental Cell Research 250, pages 576-580 (1999), which is hereby incorporated herein by reference in its entirety.